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GLI2-Mediated Melanoma Invasion and Metastasis

Alexaki, Vasileia-Ismini ; Javelaud, Delphine ; Van Kempen, Leon C. L. ; Mohammad, Khalid S. ; Dennler, Sylviane ; Luciani, Flavie ; Hoek, Keith S. ; Juàrez, Patricia ; Goydos, James S. ; Fournier, Pierrick J. ; Sibon, Claire ; Bertolotto, Corine ; Verrecchia, Franck ; Saule, Simon ; Delmas, Veronique ; Ballotti, Robert ; Larue, Lionel ; Saiag, Philippe ; Guise, Theresa A. ; Mauviel, Alain

In: Journal of the National Cancer Institute, 2010, vol. 102, no. 15, p. 1148-1159

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    Titre
    • GLI2-Mediated Melanoma Invasion and Metastasis
    Auteur
    • Alexaki, Vasileia-Ismini. Affiliations of authors: INSERM U697, Paris, France (V-IA, DJ, SD, FV, AM); Institut Curie, Centre de Recherche, Orsay, France (DJ, SD, FL, SS, VD, LL, AM); INSERM U1021, Orsay, France (DJ, SD, FL, SS, VD, LL, AM); CNRS UMR3347, Orsay, France (DJ, SD, FL, SS, VD, LL, AM); Université Paris XI, Orsay, France (DJ, SD, FL, SS, VD, LL, AM); Department of Pathology, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands (LCLVK); Division of Endocrinology, Department of Medicine, Indiana University, IUPUI, Indianapolis, IN (KSM, PJ, PJF, TAG); Department of Dermatology, University Hospital of Zurich, Zurich, Switzerland (KH); Department of Surgery, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ (JSG); Service de Dermatologie, Hôpital Ambroise Paré, Boulogne, France (CS, PS); INSERM U895, Nice, France (CB, RB)
    • Javelaud, Delphine. Affiliations of authors: INSERM U697, Paris, France (V-IA, DJ, SD, FV, AM); Institut Curie, Centre de Recherche, Orsay, France (DJ, SD, FL, SS, VD, LL, AM); INSERM U1021, Orsay, France (DJ, SD, FL, SS, VD, LL, AM); CNRS UMR3347, Orsay, France (DJ, SD, FL, SS, VD, LL, AM); Université Paris XI, Orsay, France (DJ, SD, FL, SS, VD, LL, AM); Department of Pathology, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands (LCLVK); Division of Endocrinology, Department of Medicine, Indiana University, IUPUI, Indianapolis, IN (KSM, PJ, PJF, TAG); Department of Dermatology, University Hospital of Zurich, Zurich, Switzerland (KH); Department of Surgery, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ (JSG); Service de Dermatologie, Hôpital Ambroise Paré, Boulogne, France (CS, PS); INSERM U895, Nice, France (CB, RB)
    • Van Kempen, Leon C. L.. Affiliations of authors: INSERM U697, Paris, France (V-IA, DJ, SD, FV, AM); Institut Curie, Centre de Recherche, Orsay, France (DJ, SD, FL, SS, VD, LL, AM); INSERM U1021, Orsay, France (DJ, SD, FL, SS, VD, LL, AM); CNRS UMR3347, Orsay, France (DJ, SD, FL, SS, VD, LL, AM); Université Paris XI, Orsay, France (DJ, SD, FL, SS, VD, LL, AM); Department of Pathology, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands (LCLVK); Division of Endocrinology, Department of Medicine, Indiana University, IUPUI, Indianapolis, IN (KSM, PJ, PJF, TAG); Department of Dermatology, University Hospital of Zurich, Zurich, Switzerland (KH); Department of Surgery, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ (JSG); Service de Dermatologie, Hôpital Ambroise Paré, Boulogne, France (CS, PS); INSERM U895, Nice, France (CB, RB)
    • Mohammad, Khalid S.. Affiliations of authors: INSERM U697, Paris, France (V-IA, DJ, SD, FV, AM); Institut Curie, Centre de Recherche, Orsay, France (DJ, SD, FL, SS, VD, LL, AM); INSERM U1021, Orsay, France (DJ, SD, FL, SS, VD, LL, AM); CNRS UMR3347, Orsay, France (DJ, SD, FL, SS, VD, LL, AM); Université Paris XI, Orsay, France (DJ, SD, FL, SS, VD, LL, AM); Department of Pathology, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands (LCLVK); Division of Endocrinology, Department of Medicine, Indiana University, IUPUI, Indianapolis, IN (KSM, PJ, PJF, TAG); Department of Dermatology, University Hospital of Zurich, Zurich, Switzerland (KH); Department of Surgery, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ (JSG); Service de Dermatologie, Hôpital Ambroise Paré, Boulogne, France (CS, PS); INSERM U895, Nice, France (CB, RB)
    • Dennler, Sylviane. Affiliations of authors: INSERM U697, Paris, France (V-IA, DJ, SD, FV, AM); Institut Curie, Centre de Recherche, Orsay, France (DJ, SD, FL, SS, VD, LL, AM); INSERM U1021, Orsay, France (DJ, SD, FL, SS, VD, LL, AM); CNRS UMR3347, Orsay, France (DJ, SD, FL, SS, VD, LL, AM); Université Paris XI, Orsay, France (DJ, SD, FL, SS, VD, LL, AM); Department of Pathology, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands (LCLVK); Division of Endocrinology, Department of Medicine, Indiana University, IUPUI, Indianapolis, IN (KSM, PJ, PJF, TAG); Department of Dermatology, University Hospital of Zurich, Zurich, Switzerland (KH); Department of Surgery, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ (JSG); Service de Dermatologie, Hôpital Ambroise Paré, Boulogne, France (CS, PS); INSERM U895, Nice, France (CB, RB)
    • Luciani, Flavie. Affiliations of authors: INSERM U697, Paris, France (V-IA, DJ, SD, FV, AM); Institut Curie, Centre de Recherche, Orsay, France (DJ, SD, FL, SS, VD, LL, AM); INSERM U1021, Orsay, France (DJ, SD, FL, SS, VD, LL, AM); CNRS UMR3347, Orsay, France (DJ, SD, FL, SS, VD, LL, AM); Université Paris XI, Orsay, France (DJ, SD, FL, SS, VD, LL, AM); Department of Pathology, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands (LCLVK); Division of Endocrinology, Department of Medicine, Indiana University, IUPUI, Indianapolis, IN (KSM, PJ, PJF, TAG); Department of Dermatology, University Hospital of Zurich, Zurich, Switzerland (KH); Department of Surgery, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ (JSG); Service de Dermatologie, Hôpital Ambroise Paré, Boulogne, France (CS, PS); INSERM U895, Nice, France (CB, RB)
    • Hoek, Keith S.. Affiliations of authors: INSERM U697, Paris, France (V-IA, DJ, SD, FV, AM); Institut Curie, Centre de Recherche, Orsay, France (DJ, SD, FL, SS, VD, LL, AM); INSERM U1021, Orsay, France (DJ, SD, FL, SS, VD, LL, AM); CNRS UMR3347, Orsay, France (DJ, SD, FL, SS, VD, LL, AM); Université Paris XI, Orsay, France (DJ, SD, FL, SS, VD, LL, AM); Department of Pathology, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands (LCLVK); Division of Endocrinology, Department of Medicine, Indiana University, IUPUI, Indianapolis, IN (KSM, PJ, PJF, TAG); Department of Dermatology, University Hospital of Zurich, Zurich, Switzerland (KH); Department of Surgery, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ (JSG); Service de Dermatologie, Hôpital Ambroise Paré, Boulogne, France (CS, PS); INSERM U895, Nice, France (CB, RB)
    • Juàrez, Patricia. Affiliations of authors: INSERM U697, Paris, France (V-IA, DJ, SD, FV, AM); Institut Curie, Centre de Recherche, Orsay, France (DJ, SD, FL, SS, VD, LL, AM); INSERM U1021, Orsay, France (DJ, SD, FL, SS, VD, LL, AM); CNRS UMR3347, Orsay, France (DJ, SD, FL, SS, VD, LL, AM); Université Paris XI, Orsay, France (DJ, SD, FL, SS, VD, LL, AM); Department of Pathology, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands (LCLVK); Division of Endocrinology, Department of Medicine, Indiana University, IUPUI, Indianapolis, IN (KSM, PJ, PJF, TAG); Department of Dermatology, University Hospital of Zurich, Zurich, Switzerland (KH); Department of Surgery, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ (JSG); Service de Dermatologie, Hôpital Ambroise Paré, Boulogne, France (CS, PS); INSERM U895, Nice, France (CB, RB)
    • Goydos, James S.. Affiliations of authors: INSERM U697, Paris, France (V-IA, DJ, SD, FV, AM); Institut Curie, Centre de Recherche, Orsay, France (DJ, SD, FL, SS, VD, LL, AM); INSERM U1021, Orsay, France (DJ, SD, FL, SS, VD, LL, AM); CNRS UMR3347, Orsay, France (DJ, SD, FL, SS, VD, LL, AM); Université Paris XI, Orsay, France (DJ, SD, FL, SS, VD, LL, AM); Department of Pathology, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands (LCLVK); Division of Endocrinology, Department of Medicine, Indiana University, IUPUI, Indianapolis, IN (KSM, PJ, PJF, TAG); Department of Dermatology, University Hospital of Zurich, Zurich, Switzerland (KH); Department of Surgery, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ (JSG); Service de Dermatologie, Hôpital Ambroise Paré, Boulogne, France (CS, PS); INSERM U895, Nice, France (CB, RB)
    • Fournier, Pierrick J.. Affiliations of authors: INSERM U697, Paris, France (V-IA, DJ, SD, FV, AM); Institut Curie, Centre de Recherche, Orsay, France (DJ, SD, FL, SS, VD, LL, AM); INSERM U1021, Orsay, France (DJ, SD, FL, SS, VD, LL, AM); CNRS UMR3347, Orsay, France (DJ, SD, FL, SS, VD, LL, AM); Université Paris XI, Orsay, France (DJ, SD, FL, SS, VD, LL, AM); Department of Pathology, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands (LCLVK); Division of Endocrinology, Department of Medicine, Indiana University, IUPUI, Indianapolis, IN (KSM, PJ, PJF, TAG); Department of Dermatology, University Hospital of Zurich, Zurich, Switzerland (KH); Department of Surgery, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ (JSG); Service de Dermatologie, Hôpital Ambroise Paré, Boulogne, France (CS, PS); INSERM U895, Nice, France (CB, RB)
    • Sibon, Claire. Affiliations of authors: INSERM U697, Paris, France (V-IA, DJ, SD, FV, AM); Institut Curie, Centre de Recherche, Orsay, France (DJ, SD, FL, SS, VD, LL, AM); INSERM U1021, Orsay, France (DJ, SD, FL, SS, VD, LL, AM); CNRS UMR3347, Orsay, France (DJ, SD, FL, SS, VD, LL, AM); Université Paris XI, Orsay, France (DJ, SD, FL, SS, VD, LL, AM); Department of Pathology, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands (LCLVK); Division of Endocrinology, Department of Medicine, Indiana University, IUPUI, Indianapolis, IN (KSM, PJ, PJF, TAG); Department of Dermatology, University Hospital of Zurich, Zurich, Switzerland (KH); Department of Surgery, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ (JSG); Service de Dermatologie, Hôpital Ambroise Paré, Boulogne, France (CS, PS); INSERM U895, Nice, France (CB, RB)
    • Bertolotto, Corine. Affiliations of authors: INSERM U697, Paris, France (V-IA, DJ, SD, FV, AM); Institut Curie, Centre de Recherche, Orsay, France (DJ, SD, FL, SS, VD, LL, AM); INSERM U1021, Orsay, France (DJ, SD, FL, SS, VD, LL, AM); CNRS UMR3347, Orsay, France (DJ, SD, FL, SS, VD, LL, AM); Université Paris XI, Orsay, France (DJ, SD, FL, SS, VD, LL, AM); Department of Pathology, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands (LCLVK); Division of Endocrinology, Department of Medicine, Indiana University, IUPUI, Indianapolis, IN (KSM, PJ, PJF, TAG); Department of Dermatology, University Hospital of Zurich, Zurich, Switzerland (KH); Department of Surgery, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ (JSG); Service de Dermatologie, Hôpital Ambroise Paré, Boulogne, France (CS, PS); INSERM U895, Nice, France (CB, RB)
    • Verrecchia, Franck. Affiliations of authors: INSERM U697, Paris, France (V-IA, DJ, SD, FV, AM); Institut Curie, Centre de Recherche, Orsay, France (DJ, SD, FL, SS, VD, LL, AM); INSERM U1021, Orsay, France (DJ, SD, FL, SS, VD, LL, AM); CNRS UMR3347, Orsay, France (DJ, SD, FL, SS, VD, LL, AM); Université Paris XI, Orsay, France (DJ, SD, FL, SS, VD, LL, AM); Department of Pathology, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands (LCLVK); Division of Endocrinology, Department of Medicine, Indiana University, IUPUI, Indianapolis, IN (KSM, PJ, PJF, TAG); Department of Dermatology, University Hospital of Zurich, Zurich, Switzerland (KH); Department of Surgery, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ (JSG); Service de Dermatologie, Hôpital Ambroise Paré, Boulogne, France (CS, PS); INSERM U895, Nice, France (CB, RB)
    • Saule, Simon. Affiliations of authors: INSERM U697, Paris, France (V-IA, DJ, SD, FV, AM); Institut Curie, Centre de Recherche, Orsay, France (DJ, SD, FL, SS, VD, LL, AM); INSERM U1021, Orsay, France (DJ, SD, FL, SS, VD, LL, AM); CNRS UMR3347, Orsay, France (DJ, SD, FL, SS, VD, LL, AM); Université Paris XI, Orsay, France (DJ, SD, FL, SS, VD, LL, AM); Department of Pathology, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands (LCLVK); Division of Endocrinology, Department of Medicine, Indiana University, IUPUI, Indianapolis, IN (KSM, PJ, PJF, TAG); Department of Dermatology, University Hospital of Zurich, Zurich, Switzerland (KH); Department of Surgery, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ (JSG); Service de Dermatologie, Hôpital Ambroise Paré, Boulogne, France (CS, PS); INSERM U895, Nice, France (CB, RB)
    • Delmas, Veronique. Affiliations of authors: INSERM U697, Paris, France (V-IA, DJ, SD, FV, AM); Institut Curie, Centre de Recherche, Orsay, France (DJ, SD, FL, SS, VD, LL, AM); INSERM U1021, Orsay, France (DJ, SD, FL, SS, VD, LL, AM); CNRS UMR3347, Orsay, France (DJ, SD, FL, SS, VD, LL, AM); Université Paris XI, Orsay, France (DJ, SD, FL, SS, VD, LL, AM); Department of Pathology, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands (LCLVK); Division of Endocrinology, Department of Medicine, Indiana University, IUPUI, Indianapolis, IN (KSM, PJ, PJF, TAG); Department of Dermatology, University Hospital of Zurich, Zurich, Switzerland (KH); Department of Surgery, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ (JSG); Service de Dermatologie, Hôpital Ambroise Paré, Boulogne, France (CS, PS); INSERM U895, Nice, France (CB, RB)
    • Ballotti, Robert. Affiliations of authors: INSERM U697, Paris, France (V-IA, DJ, SD, FV, AM); Institut Curie, Centre de Recherche, Orsay, France (DJ, SD, FL, SS, VD, LL, AM); INSERM U1021, Orsay, France (DJ, SD, FL, SS, VD, LL, AM); CNRS UMR3347, Orsay, France (DJ, SD, FL, SS, VD, LL, AM); Université Paris XI, Orsay, France (DJ, SD, FL, SS, VD, LL, AM); Department of Pathology, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands (LCLVK); Division of Endocrinology, Department of Medicine, Indiana University, IUPUI, Indianapolis, IN (KSM, PJ, PJF, TAG); Department of Dermatology, University Hospital of Zurich, Zurich, Switzerland (KH); Department of Surgery, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ (JSG); Service de Dermatologie, Hôpital Ambroise Paré, Boulogne, France (CS, PS); INSERM U895, Nice, France (CB, RB)
    • Larue, Lionel. Affiliations of authors: INSERM U697, Paris, France (V-IA, DJ, SD, FV, AM); Institut Curie, Centre de Recherche, Orsay, France (DJ, SD, FL, SS, VD, LL, AM); INSERM U1021, Orsay, France (DJ, SD, FL, SS, VD, LL, AM); CNRS UMR3347, Orsay, France (DJ, SD, FL, SS, VD, LL, AM); Université Paris XI, Orsay, France (DJ, SD, FL, SS, VD, LL, AM); Department of Pathology, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands (LCLVK); Division of Endocrinology, Department of Medicine, Indiana University, IUPUI, Indianapolis, IN (KSM, PJ, PJF, TAG); Department of Dermatology, University Hospital of Zurich, Zurich, Switzerland (KH); Department of Surgery, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ (JSG); Service de Dermatologie, Hôpital Ambroise Paré, Boulogne, France (CS, PS); INSERM U895, Nice, France (CB, RB)
    • Saiag, Philippe. Affiliations of authors: INSERM U697, Paris, France (V-IA, DJ, SD, FV, AM); Institut Curie, Centre de Recherche, Orsay, France (DJ, SD, FL, SS, VD, LL, AM); INSERM U1021, Orsay, France (DJ, SD, FL, SS, VD, LL, AM); CNRS UMR3347, Orsay, France (DJ, SD, FL, SS, VD, LL, AM); Université Paris XI, Orsay, France (DJ, SD, FL, SS, VD, LL, AM); Department of Pathology, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands (LCLVK); Division of Endocrinology, Department of Medicine, Indiana University, IUPUI, Indianapolis, IN (KSM, PJ, PJF, TAG); Department of Dermatology, University Hospital of Zurich, Zurich, Switzerland (KH); Department of Surgery, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ (JSG); Service de Dermatologie, Hôpital Ambroise Paré, Boulogne, France (CS, PS); INSERM U895, Nice, France (CB, RB)
    • Guise, Theresa A.. Affiliations of authors: INSERM U697, Paris, France (V-IA, DJ, SD, FV, AM); Institut Curie, Centre de Recherche, Orsay, France (DJ, SD, FL, SS, VD, LL, AM); INSERM U1021, Orsay, France (DJ, SD, FL, SS, VD, LL, AM); CNRS UMR3347, Orsay, France (DJ, SD, FL, SS, VD, LL, AM); Université Paris XI, Orsay, France (DJ, SD, FL, SS, VD, LL, AM); Department of Pathology, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands (LCLVK); Division of Endocrinology, Department of Medicine, Indiana University, IUPUI, Indianapolis, IN (KSM, PJ, PJF, TAG); Department of Dermatology, University Hospital of Zurich, Zurich, Switzerland (KH); Department of Surgery, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ (JSG); Service de Dermatologie, Hôpital Ambroise Paré, Boulogne, France (CS, PS); INSERM U895, Nice, France (CB, RB)
    • Mauviel, Alain. Affiliations of authors: INSERM U697, Paris, France (V-IA, DJ, SD, FV, AM); Institut Curie, Centre de Recherche, Orsay, France (DJ, SD, FL, SS, VD, LL, AM); INSERM U1021, Orsay, France (DJ, SD, FL, SS, VD, LL, AM); CNRS UMR3347, Orsay, France (DJ, SD, FL, SS, VD, LL, AM); Université Paris XI, Orsay, France (DJ, SD, FL, SS, VD, LL, AM); Department of Pathology, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands (LCLVK); Division of Endocrinology, Department of Medicine, Indiana University, IUPUI, Indianapolis, IN (KSM, PJ, PJF, TAG); Department of Dermatology, University Hospital of Zurich, Zurich, Switzerland (KH); Department of Surgery, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ (JSG); Service de Dermatologie, Hôpital Ambroise Paré, Boulogne, France (CS, PS); INSERM U895, Nice, France (CB, RB)
    Type de document
    • Postprint
    Langue
    • Anglais
    Publié dans
    • Journal of the National Cancer Institute, 2010, vol. 102, no. 15, p. 1148-1159. Oxford University Press
    Autre version électronique
    Classification
    • Santé
    Mots clés
    Identifiant OAI-PMH
    • oai:doc.rero.ch:296287
    Summary
    Background The transforming growth factor-β (TGF-β) pathway, which has both tumor suppressor and pro-oncogenic activities, is often constitutively active in melanoma and is a marker of poor prognosis. Recently, we identified GLI2, a mediator of the hedgehog pathway, as a transcriptional target of TGF-β signaling. Methods We used real-time reverse transcription-polymerase chain reaction (RT-PCR) and western blotting to determine GLI2 expression in human melanoma cell lines and subsequently classified them as GLI2high or as GLI2low according to their relative GLI2 mRNA and protein expression levels. GLI2 expression was reduced in a GLI2high cell line with lentiviral expression of short hairpin RNA targeting GLI2. We assessed the role of GLI2 in melanoma cell invasiveness in Matrigel assays. We measured secretion of matrix metalloproteinase (MMP)-2 and MMP-9 by gelatin zymography and expression of E-cadherin by western blotting and RT-PCR. The role of GLI2 in development of bone metastases was determined following intracardiac injection of melanoma cells in immunocompromised mice (n = 5-13). Human melanoma samples (n = 79) at various stages of disease progression were analyzed for GLI2 and E-cadherin expression by immunohistochemistry, in situ hybridization, or RT-PCR. All statistical tests were two-sided. Results Among melanoma cell lines, increased GLI2 expression was associated with loss of E-cadherin expression and with increased capacity to invade Matrigel and to form bone metastases in mice (mean osteolytic tumor area: GLI2high vs GLI2low, 2.81 vs 0.93 mm2, difference = 1.88 mm2, 95% confidence interval [CI] = 1.16 to 2.60, P < .001). Reduction of GLI2 expression in melanoma cells that had expressed high levels of GLI2 substantially inhibited both basal and TGF-β-induced cell migration, invasion (mean number of Matrigel invading cells: shGLI2 vs shCtrl (control), 52.6 vs 100, difference = 47.4, 95% CI = 37.0 to 57.8, P = .024; for shGLI2 + TGF-β vs shCtrl + TGF-β, 31.0 vs 161.9, difference = −130.9, 95% CI = −96.2 to −165.5, P = .002), and MMP secretion in vitro and the development of experimental bone metastases in mice. Within human melanoma lesions, GLI2 expression was heterogeneous, associated with tumor regions in which E-cadherin was lost and increased in the most aggressive tumors. Conclusion GLI2 was directly involved in driving melanoma invasion and metastasis in this preclinical study